Biocompatible hydrophilic polyethylene glycol (PEG) is widely used in biomedical applications, such as drug or gene delivery, tissue engineering or as an antifouling component in biomedical devices. Experimental studies have shown that the size of PEG can weaken polycation–polyanion interactions, like those between branched polyethyleneimine (b-PEI) and DNA in gene carriers, but details of its cause and underlying interactions on the atomic scale are still not clear. To better understand the interaction mechanisms in the formation of polyplexes between b-PEI-PEG based carriers and DNA, we have used a combination of in silico tools and experiments on three multicomponent systems differing in PEG MW. Using the PEI-PEG-squalene-dsDNA systems of the same size, both in the all-atom MD simulations and in experimental in-gel electrophoresis measurements, we found that the binding between DNA and the vectors is highly influenced by the size of PEG, with the binding efficiency increasing with a shorter PEG length. The mechanism of how PEG interferes with the binding between PEI and DNA is explained using a two-step MD simulation protocol that showed that the DNA–vector interactions are influenced by the PEG length due to the hydrogen bond formation between PEI and PEG. Although computationally demanding we find it important to study molecular systems of the same size both in silico and in a laboratory and to simulate the behaviour of the carrier prior to the addition of bioactive molecules to understand the molecular mechanisms involved in the formation of the polyplex.

中文翻译：

---

PEI-PEG-角鲨烯-dsDNA 复合物形成的计算机模拟研究：PEG 长度在 PEI 与 DNA 结合中的微妙作用

生物相容性亲水聚乙二醇 (PEG) 广泛用于生物医学应用，例如药物或基因传递、组织工程或作为生物医学设备中的防污成分。实验研究表明，PEG 的大小可以削弱聚阳离子-聚阴离子的相互作用，如支化聚乙烯亚胺 (b-PEI) 与基因载体中 DNA 之间的相互作用，但其原因的细节和原子尺度上的潜在相互作用仍不清楚。为了更好地理解基于B-PEI-PEG的载体和DNA之间复合物的形成的相互作用的机制，我们使用的组合，在硅片PEG MW 不同的三种多组分系统的工具和实验。使用相同大小的 PEI-PEG-squalene-dsDNA 系统，在全原子 MD 模拟和实验凝胶电泳测量中，我们发现 DNA 和载体之间的结合受 PEG 大小的影响很大, 结合效率随着 PEG 长度的缩短而增加。使用两步 MD 模拟方案解释了 PEG 如何干扰 PEI 和 DNA 之间结合的机制，该方案表明，由于 PEI 和 PEG 之间形成氢键，DNA-载体相互作用受 PEG 长度的影响。尽管在计算上要求很高，但我们发现在计算机上研究相同大小的分子系统很重要 并在实验室中模拟载体在添加生物活性分子之前的行为，以了解参与形成复合物的分子机制。